Precompetitive Collaboration Research Articles

Data Commoning in the Life Sciences

Datafication is driving organizations to invest in data commons, not only to share the costs of data generation, analysis, and curation but, more importantly, to realize synergies in precompetitive research collaborations where private and public motives interact (i.e., semicommons). The fanfare surrounding datafication often hails the sophisticated algorithms used to develop large quantities of data toward greater insight, naively assuming that more data equals better data. Yet for datafication in general and precompetitive research specifically, less attention is awarded to what actually constitutes data and evidence in the first place—that is, to its genesis, construction, and interpretation by heterogeneous scientific and commercial entities. We present the case of Open Targets, a precompetitive collaboration in the life sciences, where publicly funded research, nonprofit foundations, and for-profit pharma collaborate to generate and share data in genomics, proteomics, and bioinformatics. We theorize about the process of data commoning, a political activity in the semicommons where data are created, evidential value is assembled, and scientific meaning converges as data travels, or journeys, across creators, validators, and users. Our findings highlight the effects of relational dynamics and the political nature of data journeys: why these dynamics form, how they are manifested in a precompetitive semicommons, and what implications this can have for the mobility of data as a shared, public good.

Accelerating Process Development and Product Formulation.

Currently, the lengthy time needed to bring new drugs to market or to implement postapproval changes causes multiple problems, such as delaying patients access to new lifesaving or life-enhancing medications and slowing the response to emergencies that require new treatments. However, new technologies are available that can help solve these problems. The January 2023 NIPTE pathfinding workshop on accelerating drug product development and approval included a session in which participants considered the current state of product formulation and process development, barriers to acceleration of the development timeline, and opportunities for overcoming these barriers using new technologies. The authors participated in this workshop, and in this article have shared their perspective of some of the ways forward, including advanced manufacturing techniques and adaptive development. In addition, there is a need for paradigm shifts in regulatory processes, increased pre-competitive collaboration, and a shared strategy among regulators, industry, and academia.

A proposed multi-domain, digital model for capturing functional status and health-related quality of life in oncology.

Whereas traditional oncology clinical trial endpoints remain key for assessing novel treatments, capturing patients' functional status is increasingly recognized as an important aspect for supporting clinical decisions and assessing outcomes in clinical trials. Existing functional status assessments suffer from various limitations, some of which may be addressed by adopting digital health technologies (DHTs) as a means of collecting both objective and self-reported outcomes. In this mini-review, we propose a device-agnostic multi-domain model for oncology capturing functional status, which includes physical activity data, vital signs, sleep variables, and measures related to health-related quality of life enabled by connected digital tools. By using DHTs for all aspects of data collection, our proposed model allows for high-resolution measurement of objective data as patients navigate their daily lives outside of the hospital setting. This is complemented by electronic questionnaires administered at intervals appropriate for each instrument. Preliminary testing and practical considerations to address before adoption are also discussed. Finally, we highlight multi-institutional pre-competitive collaborations as a means of successfully transitioning the proposed digitally enabled data collection model from feasibility studies to interventional trials and care management.

Advancing digital innovation to improve equity and reduce financial toxicity in cancer treatment.

e18644 Background: The global burden of cancer is set to increase by more than 60% (to 29.4 million cases) by 2040 . Certain subgroups of patients experience avoidable disparities in access to specialized cancer treatment and discrepancies in clinical outcomes following treatment. The risk of financial toxicity following a cancer diagnosis is also not equally distributed . These disparities in cancer disease burden, treatment, and the risk of financial toxicity have the potential to be disintermediated by digital innovation. Methods: The Digital Medicine Society and Moffitt Cancer Center are co-hosting a pre-competitive collaboration to define the value of digital innovation in cancer treatment, address methodological and implementation gaps, and develop best practices for equitable adoption of digital health technologies at scale in precision oncology. We undertook a landscape review to identify and prioritize causes of disparities and financial toxicity and to benchmark the clinical, engineering, and implementation science dimensions relevant to enhanced digital innovation in cancer treatment. We convened and synthesized information from an expert roundtable which focused on challenges preventing the effective implementation of digital solutions as well as the infrastructure, payment, policy, and regulatory changes needed to promote equity and address financial toxicity with digital health tools. Results: We outline the value of digital innovation in cancer treatment and present consensus-based recommendations from workgroup convening about how digital health tools can be implemented to: Reduce costs associated with advanced cancer treatment and ameliorate disparities in cancer burden by equitably supporting early detection and cancer prevention   Advance precision oncology, minimize the costs of delays in accessing the right care and ensure that the best outcomes are available to all cancer patients  Reduce disparities in access by extending the best specialist expertise and clinical trial opportunities to all cancer patients . Conclusions: Innovative digital approaches have yet to be applied at scale to minimize the burden of financial toxicity to patients with cancer and to reduce healthcare access and outcomes disparities. The delivery of high-quality precision cancer care for all patients depends on our collective ability to increase access to specialized care, harness flows of existing patient data and the power of decentralized clinical trials, and reduce the impact of social determinants of health on patient outcomes. There is substantial opportunity to leverage the results of this landscape review and convening to 1) build impact models that articulate the value of implementing fit-for-purpose digital solutions to promote equity and reduce financial toxicity, and 2) develop implementation toolkits for the equitable and effective deployment of those solutions.

Digital technologies: Innovations that transform the face of drug development.

Recently, digital health technologies (DHTs) and digital biomarkers have gained a lot of traction in clinical investigations, motivating sponsors, investigators, and regulators to discuss and implement integrated approaches for deploying DHTs. These new tools present new and unique challenges for optimal technology integration in clinical trial processes, including operational, ethical, and regulatory issues. In this paper, we gathered different perspectives to discuss challenges and perspectives from three different stakeholders: industry, US regulators, and a public-private partnership consortium. The complexities of DHT implementation, which include regulatory definitions, defining the scope of validation experiments, and the need for partnerships between BioPharma and the technology sectors, are highlighted. Most of these challenges are related to translation of DHT-derived measures into endpoints that are meaningful to clinicians and patients, participant safety, training, and retention and privacy of data. The example of the Wearable Assessments in the Clinic and Home in PD (WATCH-PD) study is discussed as an example that demonstrated the advantages of pre-competitive collaborations, which include early regulatory feedback, data sharing, and multistakeholder alignment. Future advances in DHTs are expected to spur device-agnostic measured development and incorporate patient reported outcomes in drug development. More efforts are needed to define validation experiments for a defined context of use, incentivize data sharing and development of data standards. Multistakeholder collaborations via precompetitive consortia will help facilitate broad acceptance of DHT-enabled measures in drug development.

Abstract 3577: A first assessment of CD8-PET/CT with 89Zr-Crefmirlimab as predictive biomarker for response to standard of care immunotherapy in patients with solid tumors

Abstract Background: Elevated levels of CD8+ tumor-infiltrating lymphocytes are associated with response to immunotherapy (IoT)1 in many indications. While immunohistochemistry (IHC) has been the method of choice to evaluate CD8+ tumor infiltration level, the utility of the CD8-PET/CT imaging method offers an attractive non-invasive alternative to biopsies, with the potential to account for both intra-patient tumor heterogeneity and lesion-specific response. Methods: Using the data from ImaginAb’s phase II trial2, we predict response to standard of care (SOC) IoT in patients with advanced solid malignancies. Solely based on CD8-PET/CT scan data, the novel method scores each identifiable lesion by using its volume as measured in the CT data, and mean CD8-PET uptake values before and 4 to 6 weeks after treatment start. All lesion scores are aggregated to compute the patient score, to be subsequently compared to the best standard RECIST evaluation. This methodology was defined and developed using data from 14 patients, and later evaluated using the whole cohort of 40 patients. Results: Despite the multiplicity of indications and SOC IoT in the patient cohort, the computed scores significantly identify and stratify responders (Complete or Partial Response, mean score = -0.78, 10 subjects) from non-responders (Stable or Progressive Disease, mean score = 0.088, 25 subjects): two sample t-test value = 5.378, p-value = 1e-05. RECIST evaluations remain too preliminary to report for 4 subjects. Furthermore, CD8-PET outcomes are available much earlier (median 35 days, median best of RECIST 105 days), which may facilitate important therapy decisions. In addition, the discriminative power between the response groups is reduced when restricting the method to either of the infiltration or lesion size measurements. This result highlights the complementarity of the two measurements. Conclusions: CD8-PET offers new non-invasive opportunities in the early discrimination of responders and non-responders to IoT as well as visualization of the heterogeneity of tumor responses to IoT, supporting its use pre-IoT and early on IoT for adult solid tumors. Acknowledgement: All the data used in this study come from clinical study 2. These data were acquired and discussed within the frame of a pre-competitive collaboration between AstraZeneca, Takeda, Pfizer and imaginAb. We want to thank the respective parties for fruitful discussions which helped us refine our analysis methodology.

Empowering drug development: Leveraging insights from imaging technologies to enable the advancement of digitalhealth technologies.

The US Food and Drug Administration (FDA) has publicly recognized the importance of improving drug development efficiency, deeming translational biomarkers a top priority. The use of imaging biomarkers has been associated with increased rates of drug approvals. An appropriate level of validation provides a pragmatic way to choose and implement these biomarkers. Standardizing imaging modality selection, data acquisition protocols, and image analysis (in ways that are agnostic to equipment and algorithms) have been key to imaging biomarker deployment. The best known examples come from studies done via precompetitive collaboration efforts, which enable input from multiple stakeholders and data sharing. Digital health technologies (DHTs) provide an opportunity to measure meaningful aspects of patient health, including patient function, for extended periods of time outside of the hospital walls, with objective, sensor-based measures. We identified the areas where learnings from the imaging biomarker field can accelerate the adoption and widespread use of DHTs to develop novel treatments. As with imaging, technical validation parameters and performance acceptance thresholds need to be established. Approaches amenable to multiple hardware options and data processing algorithms can be enabled by sharing DHT data and by cross-validating algorithms. Data standardization and creation of shared databases will be vital. Pre-competitive consortia (public-private partnerships and professional societies that bring together all stakeholders, including patient organizations, industry, academic experts, and regulators) will advance the regulatory maturity of DHTs in clinical trials.

How do companies implement their zero-deforestation commitments

More than 500 companies engaged in supply chains of forest-risk commodity have adopted zero-deforestation commitments (ZDCs). We use corporate social responsibility strategy and policy implementation theories to analyse the processes and conditions for ZDC implementation. We base our study on 35 semi-structured interviews with company representatives and sector actors, publicly available ZDC data, and company reports. The objective is to understand the opportunities and challenges of ZDC implementation at the level of companies. While past research addressed ZDC coverage and effectiveness, knowledge is still lacking on companies' perspectives on the implementation of their commitments. This study provides a unique perspective by integrating the direct experience and knowledge of private actors on an environmental governance regime. We find that companies see implementation of ZDCs as a journey and often rely on voluntary sustainability standards, aligning their strategies and key performance indicators (KPIs) to these. They engage directly in the supply chain, conducting projects “on-the-ground.” Implementing ZDCs requires the involvement of procurement departments and upper management, and collaborations within and between companies. Companies rely on service providers for in-depth knowledge and field implementation. They use monitoring tools, e.g. remote sensing, and see supply chain traceability as a prerequisite for implementation. Companies face numerous implementation challenges. Internally, companies often lack leadership on their ZDC, struggle to align commitments with the organization's operations and to manage suppliers, especially smallholders, and allocate insufficient resources. Externally, they lack common standards and stakeholder support, and face challenging regulatory conditions and missing market incentives. An uneven playing field creates leakage markets. Companies identify better leadership, technology and pre-competitive collaboration as potential solutions. Zero-deforestation commitments are unlikely to greatly contribute to reducing deforestation until better implementation processes, mechanisms, and conditions are in place.

THE FUTURE OF COLLABORATIVE LEADERSHIP—HOW BUSINESS DRIVES GROWTH BY SOLVING TODAY’S CRITICAL CHALLENGES

AbstractThe author examines a world in environmental crisis, and how businesses can work with other sectors of society to make meaningful changes that will benefit humanity, now and in the future. As he writes, “People’s fates and the planet’s fate are inextricably bound.” He continues that the “world’s most sustainable brands, such as the US’s Patagonia, the UK’s Unilever; Denmark’s Ørsted, France’s BNP Parabas, and Brazil’s Natura & Co Holding SA, among many others, understand better than anyone that you can grow your business even as you wholly commit to humanity and the planet—even during this unprecedented confluence of crises.” We have to go beyond sustainability to what he terms “Lead With We” collaboration. He writes that “at the core of the Lead With We business paradigm is the prescription of a “Virtuous” Spiral of Collectivized Purpose in Action.” He describes in detail how this works for six different, yet related entities: Business, Investors, Government, Civil Society, Philanthropy, and Competitors. Within the latter, he writes, “Great corporate precedents for pre‐competitive collaboration (PCC) including New Zealand newbie, Allbirds, which open‐sourced its carbon‐free sneaker tech to its whole industry. Honest Tea and Safeway partnered; UPS and DHL; Google and Yahoo!; Ford and GM//General Motors; Apple and Samsung.”

Diversity and Inclusion in Drug Development: Rethinking Intrinsic and Extrinsic Factors with Patient Centricity.

Diversity and Inclusion in Drug Development: Rethinking Intrinsic and Extrinsic Factors with Patient Centricity.

The Role of Food and Beverage Companies in Transforming Food Systems: Building Resilience at Multiple Scales.

Food and beverage companies are increasingly aware of the risks posed by climate change and many are interested in addressing them by building resilience along their supply chains. Financial incentives for environmental, social, and governance criteria further motivate mitigation action by firms. To achieve sustainable outcomes, human and ecological systems must be managed for resilience. The scientific community and food and beverage firms must collaborate in the development of measurable and verifiable indicators that support adaptation and mitigation action along food supply chains. This article identifies 3 areas in which a synergistic progress would set a resilient trajectory toward sustainability: 1) incentives for sustainable intensification, 2) expanded reporting standards, and 3) pre-competitive collaborations. Incremental, clear, and measurable steps can be taken to adapt food supply chains to the pressing challenges imposed by climate change, mitigate further emissions, and bring producers and consumers along in the journey towards planetary health.

Precompetitive Collaborations in the Pharmaceutical Industry: Process Safety Groups Work Together to Reduce Hazards, from R&D Laboratories to Manufacturing Facilities

Precompetitive Collaborations in the Pharmaceutical Industry: Process Safety Groups Work Together to Reduce Hazards, from R&D Laboratories to Manufacturing Facilities

Advancing human genetics research and drug discovery through exome sequencing of the UK Biobank.

The UK Biobank Exome Sequencing Consortium (UKB-ESC) is a private-public partnership between the UK Biobank (UKB) and eight biopharmaceutical companies that will complete the sequencing of exomes for all ~500,000 UKB participants. Here, we describe the early results from ~200,000 UKB participants and the features of this project that enabled its success. The biopharmaceutical industry has increasingly used human genetics to improve success in drug discovery. Recognizing the need for large-scale human genetics data, as well as the unique value of the data access and contribution terms of the UKB, the UKB-ESC was formed. As a result, exome data from 200,643 UKB enrollees are now available. These data include ~10 million exonic variants-a rich resource of rare coding variation that is particularly valuable for drug discovery. The UKB-ESC precompetitive collaboration has further strengthened academic and industry ties and has provided teams with an opportunity to interact with and learn from the wider research community.

Sustainability in supply chains: reappraising business process management

In the context of sustainable supply chain management (SSCM), business processes that enable process integration have been explored in a limited way. This paper offers empirical data in response to this gap by evidencing business processes that create sustainability value in the context of the supply chain—and, the role of a phased approach as an enabler. The data are derived from a case study (of 52 organisations) based on a sustainable cocoa supply chain network and the key business processes across that network. Eight business processes were identified as critical to SSCM—strategic planning, design, governance, integration, collaboration, pre-competitive collaboration, stakeholder management, and performance monitoring and evaluation. We demonstrate how business processes become bespoke sustainability processes in relation to SCM through a phased approach of alignment, implementation and maintenance.

Validation of ctDNA Quality Control Materials Through a Precompetitive Collaboration of the Foundation for the National Institutes of Health.

PURPOSEWe report the results from a Foundation for the National Institutes of Health Biomarkers Consortium project to address the absence of well-validated quality control materials (QCMs) for circulating tumor DNA (ctDNA) testing. This absence is considered a cause of variance and inconsistencies in translating ctDNA results into clinical actions.METHODSIn this phase I study, QCMs with 14 clinically relevant mutations representing single nucleotide variants, insertions or deletions (indels), translocations, and copy number variants were sourced from three commercial manufacturers with variant allele frequencies (VAFs) of 5%, 2.5%, 1%, 0.1%, and 0%. Four laboratories tested samples in quadruplicate using two allele-specific droplet digital polymerase chain reaction and three (amplicon and hybrid capture) next-generation sequencing (NGS) panels.RESULTSThe two droplet digital polymerase chain reaction assays reported VAF values very close to the manufacturers’ claimed concentrations for all QCMs. NGS assays reported most single nucleotide variants and indels, but not translocations, close to the expected VAF values. Notably, two NGS assays reported lower VAF than expected for all translocations in all QCM mixtures, possibly related to technical challenges detecting these variants. The ability to call ERBB2 copy number amplifications varied across assays. All three QCMs provided valuable insight into assay precision. Each assay across all variant types demonstrated dropouts at 0.1%, suggesting that the QCM can serve for testing of an assay’s limit of detection with confidence claims for specific variants.CONCLUSIONThese results support the utility of the QCM in testing ctDNA assay analytical performance. However, unique designs and manufacturing methods for the QCM, and variations in a laboratory’s testing configuration, may require testing of multiple QCMs to find the best reagents for accurate result interpretation.

The role of digital clinical measures in improving cancer care and research.

e13584 Background: From objectively assessing performance status to recording simple vital signs, the adoption of high quality digital clinical measures offers enormous possibilities for transforming cancer care & research. However, the development & deployment of high quality digital measures in oncology lags behind adoption in other therapeutic areas. At the time of submission, the DiMe library of digital endpoints reports 166 unique digital endpoints being used in industry sponsored trials of new medical products, but none are being used in an oncology trial. There are seven digital clinical measures working their way through the FDA qualification program, but none in oncology. During the pandemic, care for patients with cardiac and other chronic conditions transitioned out of the clinic & into the home powered not only by virtual visits, but high quality information from remote monitoring. A study of oncology care facilities worldwide reported 89% finding difficulty in delivering usual care due to the challenges of safely bringing patients into the clinic during COVID. Methods: From March to Sep 2020, cross-industry stakeholders at the Digital Medicine Society (DiMe), Elektra Labs, Genentech, Koneksa, Myokardia, Sage Bionetworks, Scripps Research, and the US Food & Drug Administration came together to synthesize best practices from the digital health field, breaking down silos to create ‘ The Playbook’, the comprehensive and accessible “how-to” guide to support all stakeholders working to advance the safe, effective, ethical, and equitable use of digital clinical measures to improve lives. In October 2020, DiMe -- a 501c3 non-profit dedicated to advancing digital medicine to improve lives -- convenened a pre-competitive collaboration of 44 participants from 29 organizations to drive the adoption of the best practices articulated in The Playbook. Results: The Playbook describes trans-industry consensus for best practices for developing and deploying digital clinical measures across patient care, clinical research, and public health, including for oncology. Conclusions: The clinical, technical, and operational best practices necessary to develop and deploy high quality digital clinical measures into cancer care & research have been established. There is no reason for their successful adoption in oncology to lag behind other therapeutic areas. The Playbook and additional resources to support implementation due for launch on April 30 are critical tools for the field of oncology.

COVID-19 vaccines and treatments: When speed is necessary and not enough.

COVID-19 vaccines and treatments: When speed is necessary and not enough.

Fit-for-Purpose Biometric Monitoring Technologies: Leveraging the Laboratory Biomarker Experience.

Biometric monitoring technologies (BioMeTs) are becoming increasingly common to aid data collection in clinical trials and practice. The state of BioMeTs, and associated digitally measured biomarkers, is highly reminiscent of the field of laboratory biomarkers 2 decades ago. In this review, we have summarized and leveraged historical perspectives, and lessons learned from laboratory biomarkers as they apply to BioMeTs. Both categories share common features, including goals and roles in biomedical research, definitions, and many elements of the biomarker qualification framework. They can also be classified based on the underlying technology, each with distinct features and performance characteristics, which require bench and human experimentation testing phases. In contrast to laboratory biomarkers, digitally measured biomarkers require prospective data collection for purposes of analytical validation in human subjects, lack well‐established and widely accepted performance characteristics, require human factor testing, and, for many applications, access to raw (sample‐level) data. Novel methods to handle large volumes of data, as well as security and data rights requirements add to the complexity of this emerging field. Our review highlights the need for a common framework with appropriate vocabulary and standardized approaches to evaluate digitally measured biomarkers, including defining performance characteristics and acceptance criteria. Additionally, the need for human factor testing drives early patient engagement during technology development. Finally, use of BioMeTs requires a relatively high degree of technology literacy among both study participants and healthcare professionals. Transparency of data generation and the need for novel analytical and statistical tools creates opportunities for precompetitive collaborations.

Remote Digital Monitoring for Medical Product Development

The use of digital health products has gained considerable interest as a new way to improve therapeutic research and development. Although these products are being adopted by various industries and stakeholders, their incorporation in clinical trials has been slow due to a disconnect between the promises of digital products and potential risks in using these new technologies in the absence of regulatory support. The Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium hosted a public workshop to address challenges and opportunities in this field. Important characteristics of tool development were addressed in a series of presentations, case studies, and open panel sessions. The workshop participants endorsed the usefulness of an evidentiary criteria framework, highlighted the importance of early patient engagement, and emphasized the potential impact of digital monitoring tools and precompetitive collaborations. Concerns were expressed about the lack of real‐life validation examples and the limitations of legacy standards used as a benchmark for novel tool development and validation. Participants recognized the need for novel analytical and statistical approaches to accommodate analyses of these novel data types. Future directions are to harmonize definitions to build common methodologies and foster multidisciplinary collaborations; to develop approaches toward integrating digital monitoring data with the totality of the data in clinical trials, and to continue an open dialog in the community. There was a consensus that all these efforts combined may create a paradigm shift of how clinical trials are planned, conducted, and results brought to regulatory reviews.

The Michael J. Fox Foundation's Strategies for Accelerating Translation of LRRK2 into Therapies for Parkinson Disease.

Since 2005, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has invested significant funding and non-funding effort to accelerate research and drug development activity around the Parkinson disease (PD)-associated protein LRRK2. MJFF has spearheaded multiple public/private pre-competitive collaborations that have contributed to our understanding of LRRK2 function; de-risked potential safety questions around the therapeutic use of LRRK2 kinase inhibitors; and generated critical research tools, biosamples, and data for the field. Several LRRK2-targeted therapies are now in human testing due to the hard work of so many in the PD community. In this perspective, we present a holistic description and model of how our Foundation’s support targeted important barriers to LRRK2 research and helped move the field into clinical trials.